From increasing evidence that blood rheology is disturbed in diabetes mellitus, and that red cell oxygen transport may also be limited, many investigators have suggested that localized hypoxia may contribute, over the years, to the establishment of diabetic microangiopathy. Because the erythrocyte is central to this hypothesis, it is the purpose of this research to examine the effects of diabetes on both the physical properties and the oxygen carrying function of the red cell, and to relate diabetic control to microvascular perfusion and tissue oxygenation in an animal model. Principal in vitro studies will include measurement of: (1) red cell deformability by the micropipette technique, as well as by filtration and cone-plate viscometry; (2) red cell and plasma factors which affect deformability; (3) oxygen delivery by flowing blood in an in vitro model which provides control of rheologic variables; and (4) factors which influence red cell oxygen transport. Additionally, imposition of metabolic stress on the diabetic erythrocyte may unmask basic underlying defects not apparent in direct studies. Finally, the level of diabetic control will be related to microcirculatory flow patterns and tissue oxygenation in diabetic rabbits with chronically-implanted, electrode-containing ear chambers. Evidence that the physical properties or oxygen carrying function of red cells are altered in diabetes would contribute to the understanding of the vascular complications of the disease. Further, identification of specific causes for these red cell abnormalities would provide new directions for research and therapeutic control.